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Massively recruited sTLR9+ neutrophils in rapidly formed nodules at the site of tumor cell inoculation and their contribution to a pro-tumor microenvironment

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Abstract

Neutrophils exert either pro- or anti-tumor activities. However, few studies have focused on neutrophils at the tumor initiation stage. In this study, we unexpectedly found a subcutaneous nodule in the groin areas of mice inoculated with tumor cells. The nodule was developed 24 h after the inoculation, filled with tumor cells and massively recruited neutrophils, being designated as tumor nodules. 22% of the neutrophils in tumor nodules are surface TLR9 (sTLR9) expressing neutrophils (sTLR9+ neutrophils). With tumor progression, sTLR9+ neutrophils were sustainably increased in tumor nodules/tumor tissues, reaching to 90.8% on day 13 after inoculation, with increased expression of IL-10 and decreased or no expression of TNFα. In vivo administration of CpG 5805 significantly reduced sTLR9 expression of the sTLR9+ neutrophils. The reduction of sTLR9 on neutrophils in tumor nodules contributed to the induction of an anti-tumor microenvironment conductive to the inhibition of tumor growth. Overall, the study provides insights for understanding the role of sTLR9+ neutrophils in the tumor development, especially in the early stage.

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Acknowledgements

We would like to thank Yunpeng Yao, Feiyu Lu, Yangeng Wang, Shujun Liu for technical assistance through the year. This study is financially supported by the National Natural Science Foundation of China (31670937).

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Authors and Affiliations

  1. Department of Immunology, College of Basic Medical Sciences, Jilin University, Changchun, 130021, Jilin, People’s Republic of China

    Mengyuan Kou, Kuo Qu & Yongli Yu

  2. Department of Molecular Biology, College of Basic Medical Sciences, Jilin University, Changchun, 130021, Jilin, People’s Republic of China

    Wenting Lu & Liying Wang

  3. Department of Developmental-Behavioral Pediatrics, The First Hospital of Jilin University, Changchun, 130021, Jilin, People’s Republic of China

    Mengru Zhu

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  1. Mengyuan Kou
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  2. Wenting Lu
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MK was the main researcher for this study including the experiment design and operation, data analysis, and manuscript writing; WL, MZ, and KQ participated in operation for some experiments including flow cytometry and mouse experiments. YY and LW provided research ideas, funds, and the writing and revising of the manuscript.

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Correspondence to Liying Wang or Yongli Yu.

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Kou, M., Lu, W., Zhu, M. et al. Massively recruited sTLR9+ neutrophils in rapidly formed nodules at the site of tumor cell inoculation and their contribution to a pro-tumor microenvironment. Cancer Immunol Immunother 72, 2671–2686 (2023). https://doi.org/10.1007/s00262-023-03451-1

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